Studies are being conducted to investigate the genetic control and biochemical basis of DNA repair and mutagenesis in Drosophila melanogaster. Strains which exhibit increased sensitivity of killing by mutagenic agents ("mus" mutants) are isolated as putative repair-defective mutants. Mus mutants are localized to specific chromosomal sites and examined for cross-sensitivity to a variety of mutagenic agents, defects in male or female fertility, alterations in meiotic nondisjunction frequencies and effects on miotic recombination ability. Studies of mutagen sensitivity of single and double mutant strains are designed to classify mus mutants to specific pathways of DNA repair. Mutagenesis experiments examine the effect of specific mus loci on induced mutation rates. Biochemical studies examined at the development of in vitro culture systems which will allow accurate analysis of DNA replication kinetics after exposure to chemical mutagens. Present experiments are focused on comparisons of replication kinetics in a variety of embryonic cell lines and isolated organ sytems. Autoradiographic studies are currently being developed to examine the DNA synthetic capacity of various cell types and their ability to perform excision repair, as measured by unscheduled DNA synthesis, after exposure to various mutagenic agents.